Non-haematopoietic stem cells obtained from bone marrow called mesenchymal stem cells (MSCs) hold great therapeutic potential in regenerative medicine and tissue engineering owing to their ability to differentiate into osteogenic, adipogenic, chondrogenic, myogenic and possibly neurogenic lineages.1,2,3 US patent publication numbers 2005/0249731, 2005/0019911 and 2003/0157078 disclose methods of isolating mesenchymal stem cells and the potential use of such cells for tissue repair.
The treatment of cardiovascular disease (CVD) represents one of the many possible target therapeutic applications of MSCs. CVD is the leading cause of death is purported to be responsible for more than 50% of all deaths in Europe. Furthermore, it is estimated that 1 in 4 US residents has CVD in one form or another. Expenditure on the treatment of CVD is estimated to be $393.5 billion (2005) in the US alone, and such figures are expected to grow as the population in Europe and the US ages. Among CVD disorders, ischemic heart disease has emerged as the primary cause of deaths worldwide.
Restoration of a vascular supply to the ischemic heart is of high clinical relevance and pro-angiogenic therapies aim to reduce morbidity and mortality rates associated with the onset of cardiovascular disease. Over the past decade there has been a huge leap in unravelling the molecular mechanisms that govern new blood vessel formation. A number of regulatory factors have been identified as key role players in the formation of blood vessels including the vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) families. This new knowledge has allowed the design and implementation of novel pro-angiogenic interventions and therapeutic approaches including gene therapy, cellular therapy and combinations of both.
Adult stem cell therapy holds great promise for cardiac repair by means of regeneration of the myocardium and neovascularisation in arterial occlusive disease. There is increasing evidence that MSCs, derived from bone marrow, can successfully be used to restore cardiac function following ischemic injury. Enhancing the ability of MSCs to promote neovascularisation in the ischemic heart could have an impact in reducing the mortality rates associated with the onset and development of cardiovascular disease.
Stem cell mediated neovascularisation has been heightened by the modification of these cells to over express angiogenic cytokines.4 Like the development steps in pro-angiogenic gene therapy, initial studies focussed on the over-expression of a single angiogenic factor. VEGF has proved popular, along with other factors such as Ang-1 and HGF, and initial pre-clinical reports point to improvements in myocardial reperfusion over cell therapy alone.5 Further studies have ultilised a multimodal approach, where a number of factors are over expressed together in MSCs resulting in further increases in global heart function.6 
Notwithstanding the state of the art it would be still be desirable to provide for alternative MSCs genetically modified to express or over-express a particular protein capable of promoting neovascularisation.